The pathogenic Neisseria are obligate human pathogens that rely on several antigenic variation systems to continually colonize and cause disease in the human population. This proposal will continue our studies into the molecular mechanisms used to promote pilin antigenic variation in Neisseria gonorrhoeae. High frequency changes in the pilin amino acid sequence are mediated by gene conversion reactions between one of 18 silent pilin copies and the single expressed pilin gene. In the next funding period we will continue to conduct our field-leading investigations into the molecular mechanisms require to effect high frequency gene conversion within the context of a bacterial chromosome. The results of these innovative studies will have great impact on the study of Neisserial pathogenesis, mechanisms of antigenic variation, DNA recombination and replication, and the role of alternative DNA structures on molecular processes in all cells.